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Genetic classification offers guide to stem cell transplantation for patients with myelodysplastic syndrome

  • R. Coleman Lindsley, MD, PhD

    A blood test can indicate whether some patients with myelodysplastic syndrome (MDS) are likely to benefit from a stem cell transplant and, if so, whether the transplant should involve high or moderate doses of chemotherapy and/or radiation therapy. The findings are according to study results to be presented by Dana-Farber Cancer Institute investigators at the 58th annual meeting of the American Society of Hematology (ASH).

    By analyzing 127 genes in blood samples from 1,514 patients and linking the results to patients’ clinical data, the researchers identified six molecular subtypes of the disease that can guide physicians in deciding the proper therapy for patients. The results will be discussed in an oral presentation at the conference.

    MDS is a family of diseases in which the bone marrow produces an insufficient supply of healthy blood cells. Although treatments vary depending on the specific type of MDS a patient has, donor stem cell transplants are generally used for patients at high risk of relapsing after standard drug therapy.

    The new study will help physicians refine treatment choices for these high-risk patients, the authors say. The investigators found that patients whose blood cells carried a mutation in the gene TP53 tended to survive less than a year after a stem cell transplant and relapsed quickly. These findings held true regardless of whether patients received a standard transplant, which involves high doses of chemotherapy and/or radiation therapy, or a reduced-intensity transplant, which uses lower doses.

    The researchers found that patients whose blood cells harbored mutations in any of eight genes involved in the RAS signaling pathway also had poor survival due to relapse, but benefited significantly from receiving a high-intensity stem cell transplant. Patients whose blood cells bore mutations in the gene JAK2 usually didn’t relapse but had a high risk of complications from the transplant itself.

    Among patients who undergo a stem cell transplant for MDS, about 20 percent have TP53 mutations, 15 percent have RAS mutations, and 2 to 3 percent have JAK2 mutations.

    “In deciding whether a stem cell transplant is appropriate for a patient with MDS, it’s always necessary to balance the potential benefit with the risk of complications,” said study lead author R. Coleman Lindsley, MD, PhD, of Dana-Farber. “Our findings will help physicians identify patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”

    The senior author of the study is Benjamin Ebert, MD, PhD, of Dana-Farber. Co-authors are Brenton Mar, MD, PhD, Robert Redd, MS, Corey Cutler, MD, MPH, Joseph Antin, MD, and Donna Neuberg, ScD, of Dana-Farber; Wael Saber, MD, MS, and Tao Wang, PhD, of the Center for International Blood and Marrow Transplant Research (CIBMTR) at the Medical College of Wisconsin; Michael Haagenson, MS, and Stephen Spellman, MBS, of CIBMTR, National Marrow Donor Program/Be The Match®, Minneapolis, Minn.; Peter Grauman, of Brigham and Women’s Hospital; Stephanie Lee, MD, of Fred Hutchinson Cancer Research Center; Michael Verneris, MD, of the University of Minnesota; Katharine Hsu, MD, PhD, of Memorial Sloan-Kettering Cancer Center; and Katharina Fleischhauer, MD, of University Hospital Essen, Essen, Germany.

  • RColeman Lindsley
  • Research
  • Stem Cell/Bone Marrow Transplant
  • Myelodysplastic/Myeloproliferative Diseases
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